Harnessing big 'omics' data and AI for drug discovery in hepatocellular carcinoma.

Journal: Nature reviews. Gastroenterology & hepatology
Published Date:

Abstract

Hepatocellular carcinoma (HCC) is the most common form of primary adult liver cancer. After nearly a decade with sorafenib as the only approved treatment, multiple new agents have demonstrated efficacy in clinical trials, including the targeted therapies regorafenib, lenvatinib and cabozantinib, the anti-angiogenic antibody ramucirumab, and the immune checkpoint inhibitors nivolumab and pembrolizumab. Although these agents offer new promise to patients with HCC, the optimal choice and sequence of therapies remains unknown and without established biomarkers, and many patients do not respond to treatment. The advances and the decreasing costs of molecular measurement technologies enable profiling of HCC molecular features (such as genome, transcriptome, proteome and metabolome) at different levels, including bulk tissues, animal models and single cells. The release of such data sets to the public enhances the ability to search for information from these legacy studies and provides the opportunity to leverage them to understand HCC mechanisms, rationally develop new therapeutics and identify candidate biomarkers of treatment response. Here, we provide a comprehensive review of public data sets related to HCC and discuss how emerging artificial intelligence methods can be applied to identify new targets and drugs as well as to guide therapeutic choices for improved HCC treatment.

Authors

  • Bin Chen
    Department of Otorhinolaryngology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, China.
  • Lana Garmire
    Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Diego F Calvisi
    Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.
  • Mei-Sze Chua
    Department of Surgery, Asian Liver Center, School of Medicine, Stanford University, Stanford, CA, USA.
  • Robin K Kelley
    Department of Medicine, University of California, San Francisco, CA, USA.
  • Xin Chen
    University of Nottingham, Nottingham, United Kingdom.